The reactions of hemeproteins and molecular oxygen will be studied with particular emphasis on the mechanisms for control of these reactions so important in the production of cellular energy and on the manner in which protein abnormalities or outside agents (e.g., pollutants, drugs, food additives, antioxidants) inhibit or otherwise perturb these reactions. The structure and reactions of cytochrome c oxidase, the major O2 utilizing and energy producing site in the cell, will be investigated within, and isolated from, heart muscle. The processes which involve reversible O2 binding, O2 transport by hemoglobin in blood and O2 storage by myoglobin in muscle, will be examined in terms of the structural basis for normal function and the causes of malfunction due to abnormal protein structure, metabolic disfunction, compounds such as CO and No that block O2 binding, and compounds such as azides, nitrites, phenols, and "oxidant drugs" that cause production of highly reactive superoxide or peroxide as well as oxidized protein. The relationship between structure and properties will be examined with protein-free natural iron porphyrin derivatives and isolated hemeproteins and then as possible, extended to subcellular material (e.g., mitochondria, microsomes) and to heart muscle, red blood cells, and other intact tissue. The physical probes to be used include infrared, nuclear magnetic resonance, electron spin resonance, Mossbauer, and ultraviolet-visible spectroscopies and magnetic susceptibility.